Effects of arsenic, a toxic oil shale constituent, on cell proliferation and histone phosphorylation. [Cultured Chinese hamster ovary cells]

Technical Report · Sat Dec 01 04:00:00 EST 1979

DOI:https://doi.org/10.2172/5522598· OSTI ID:5522598

Gurley, L R; Walters, R A; Jett, J H; Tobey, R A

Because of the casual association between arsenic and cancer in man, studies were initiated to determine if subtoxic levels of arsenic have effects on cell proliferation and chromatin constituents. Cultured CHO cells were treated with both As(III) and As(V), as sodium arsenite (NaAsO/sub 2/) and sodium arsenate (Na/sub 2/HAsO/sub 4/), respectively, to assess their biological impact. Quantitatively, arsenite was ten times more toxic than arsenate, with 5 x 10/sup -5/ M arsenite causing irreversible inhibition of culture growth. At subtoxic concentrations, 10/sup -5/ M NaAsO/sub 2/ induced culture growth kinetics that caused a cell division delay period followed by a spontaneous recovery of cell division. During this division delay, histone Hl phosphorylation was reduced to 40% of control. It then recovered to control levels just before recovery of cell division. Histone H2A phosphorylation was stimulated in the middle of the division delay period, followed by a stimulation of H3 phosphorylation just before recovery of cell division. The DNA synthesis rate was also reduced during division delay, but it did not recover before resumption of cell division. The ATP pool levels were unaffected at these low arsenite concentrations. Flow microfluorometric analysis demonstrated that cell-cycle progression was inhibited throughout the entire cycle during the division delay period. Upon recovery of cell division, cells in S and G/sub 2/ regained the capacity to resume cycle traverse earlier than did cells in G/sub 1/. These results support the conclusions that interphase Hl phosphorylation is not tightly coupled to DNA synthesis, but is vitally involved in cell-cycle progression. The results indicate that sodium arsenite modulates those histone phosphorylations involved with cell proliferation.

• Research Organization: Los Alamos Scientific Lab., NM (USA)
• DOE Contract Number: W-7405-ENG-36
• OSTI ID: 5522598
• Report Number(s): LA-8063-MS
• Country of Publication: United States
• Language: English

Related Subjects

550300 -- Cytology
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALI METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
ARSENATES
ARSENIC
ARSENIC COMPOUNDS
ARSENIC OXIDES
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
CELL CULTURES
CELL CYCLE
CELL DIVISION
CELL PROLIFERATION
CHALCOGENIDES
CHEMICAL REACTIONS
CHRONIC EXPOSURE
DATA
DATA FORMS
DNA REPLICATION
DOSE-RESPONSE RELATIONSHIPS
ELEMENTS
EXPERIMENTAL DATA
HAMSTERS
HISTONES
INFORMATION
INHIBITION
ISOLATED VALUES
MAMMALS
NUCLEIC ACID REPLICATION
NUMERICAL DATA
ORGANIC COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
PHOSPHORYLATION
PROTEINS
RECOVERY
RODENTS
SEMIMETALS
SODIUM COMPOUNDS
VALENCE
VERTEBRATES